The present invention relates to a method of and a device for dry application of substances, particularly marker substances and/or active substances, on inhalable pulverulent carrier substances.
Inhalable dry powders are partly made of lactose, liposomes or other carrier substances. For checking the quantity of particles deposited in the lung it has been known to apply a marker on these pulverulent carrier substances or aerosol particles, respectively, which can be established in terms of position and distribution from outside the lung. To this end, normally radioactive substances such as sodium per-technetate (99mTc) Tc04 are used. Beyond that, however, it will also be possible in the future to use magnetic markers or contrast media which can be detected by means of nuclear magnetic resonance spectrography (NMR). It is also possible to apply minute quantities of active substances, especially medicaments, on pulverulent inhalable carrier substances, instead of this marker of pulverulent carrier substances for the external detection of the quantities of particles which have been deposited in the lung. Moreover, the application of such active substances in small quantities may be combined with a marker.
So far, it is not yet known to apply marker substances and/or active substances on inhalable pulverulent carrier substances in a dry form. It is common to introduce the small particles of the pulverulent carrier substance into a solution in which the marker substance is contained and then dried. This entails the inexpedient problem that particularly with water-soluble substances or carrier substances, respectively, the properties of the carrier substance particles are lost or that these particles dissolve completely.
The invention is now based on the problem of rendering a method and a device of the type available which has been outlined by way of introduction, wherein the conservation of the inhalable pulverulent carrier substances and their properties is achieved when marker substances and/or active substances are applied.
In accordance with the invention this problem is solved in terms of a method by the features defined in Patent Claim 1. Preferred features constituting an expedient improvement of this method are defined in the dependent method claims 2 to 5.
This problem is solved in terms of a device by the features defined in Patent claim 6. Preferred further embodiments of the invention are defined in the dependent device claims.
In accordance with the inventive method, as illustrated in FIG. 6, the dry application of substances provided in step S1 on inhalable pulverulent carrier substances is realized by provided in step S2 by initially dissolving the substance to be applied to a liquid in step S3, by subsequently vaporizing the fluid in step S4, and by drying the aerosol droplets to so formed completely for generating aerosol particles in step S5. Then a whirling contact to the aerosol particles with the pulverulent carrier substance is established in step S7, with the fine aerosol particles expediently adhering to the particles to be marked.
In accordance with a preferred embodiment of the invention, the moisture of the aerosol particles is controlled prior to the whirling contact in step S7, so as to avoid any influence on the power particles to be marked in the pulverulent carrier substances, with the moisture of the aerosol particles being preferably checked in step S6 and subject to further vaporization until the moisture is adapted tot he respective carrier substance.
In correspondence with a preferred embodiment of the inventive method, the whirling contact is realized by aspiration of circulated aerosol particles through the carrier substance, with the aspiration of the aerosol particles being preferably performed via a retaining filter. In this manner, the pulverulent carrier substance is whirled up expediently, and due to the circulated aerosol particles, which are transferred in a manner similar to that in a cyclone separator, a particularly intimate mixing and the desired dry application of the marker substances and/or active substances is achieved.
According to the inventive device an aerosol generator and a mixing chamber are provided as apparatus elements, with the aerosol generator comprising a nozzle vaporizer for the substance to be applied and dissolved in a liquid, as well as a means for drying the aerosol particles so formed. The mixing chamber serves to receive pulverulent carrier substance and to establish the whirling with dry aerosol particles introduced by circulation.
The substance, for instance sodium per-technetate, which is to be used for marking the pulverulent carrier substances, is dissolved in a liquid such as water or alcohol, with vaporization taking place in the aerosol generator by means of a conventional jet-type or ultrasonic vaporizer. The vaporization may be performed with any system whatsoever which permits the formation of an aerosol from a liquid. The aerosol generator has expediently a large volume and contains a desiccant such as silica gel, for drying the aerosol droplets generated completely before they leave the aerosol generator. In this manner it is possible to produce very small aerosol particles having a particle size in the range from 1 nm to 500 nm.
These dry aerosol particles are then introduced into the joining mixing chamber where the inhalable pulverulent carrier substance is contained on which the dry aerosol particles are to be applied.
For the introduction of dry aerosol particles and for whirling in the mixing chamber a vacuum pump is provided in correspondence with a preferred embodiment, which pump is connected to the mixing chamber via a filter array. Due to the eccentric introduction of the dry aerosol particles into the mixing chamber that is preferably provided in the lower region of the mixing chamber with an oblique downward orientation, which is moreover expediently provided, the inhalable pulverulent carrier substance is whirled up and the fine aerosol particles adhere to the pulverulent particles of the carrier substance.
For checking the moisture of the dried aerosol particles preferably a moisture sensor is provided, particularly a hygrometer, which moisture sensor is preferably disposed in a connecting line between the aerosol generator and the mixing chamber, and preferably the moisture of the dried aerosol particles can be adjusted for adaptation to the respective carrier substance by means of an appropriate on/off operation of the nozzle-type vaporizer in the aerosol generator.
In accordance with another preferred embodiment of the invention, the mixing chamber is adapted to be closed and sealed by means of a cover including an opening connector for the connection of a vacuum pump, with the cover being adapted for being partly inserted into an upper section of the mixing chamber and for being fastened on the mixing chamber by means of a swivel nut. With these provisions the mixing chamber can be easily charged with the inhalable pulverulent carrier substance for preparing the dry application of substances, and can be discharged after application without any problems.
In correspondence with another preferred embodiment of the invention a filter array is provided between the cover and the mixing chamber, which filter array presents a structure consisting of a fine filter having a mesh size of roughly 1-3 xcexcm, preferably in the form of a cellulose filter, and a supporting filter having a high strength and a mesh size between 50 and 500 xcexcm, preferably in the form of a metal sheet. The fine filter expediently prevents the escape of powder from the mixing chamber and is protected from tearing by the supporting filter which contacts the fine filter on the side facing the vacuum pump.
According to another embodiment of the invention the aerosol generator is provided for producing a particle size of  less than 0.5 xcexcm at a relative moisture of  less than 50%, preferably  less than 30%.